Lower Parkinson's Risk in Patients on Ibuprofen

Patients who took ibuprofen for long periods of time were less likely to be diagnosed with Parkinson's disease later, researchers say.

No such relationship was seen for other common pain relievers including aspirin or acetaminophen, according to the analysis of six years of data on some 136,000 participants in the Nurses' Health Study and the Health Professionals Follow-Up Study, published online in Neurology.

According to Dr. Xiang Gao of Brigham and Women's Hospital in Boston and colleagues, those taking ibuprofen at least twice a week had about a 40 percent lower risk for developing Parkinson's.

But neither the study authors nor other researchers suggested that people should start taking ibuprofen to ward off Parkinson's disease on the basis of these findings.

In an accompanying editorial, Dr. James H. Bower of the Mayo Clinic in Rochester, Minn., and Dr. Beate Ritz of the University of California Los Angeles, scoffed at the idea.

They likened the study's finding to earlier results showing that hyperuricemic patients have lower rates of Parkinson's disease.

"Are we ready to tell our patients with Parkinson's disease that they should start taking ibuprofen? Absolutely not. Nor should we tell them to start smoking, drinking coffee, and eating liver paté in hopes of developing gout," they wrote.

The editorial reminded readers that ibuprofen has significant, well-known risks including liver toxicity and gastric ulcers.

"This represents another in a long line of ... epidemiological studies which purport to demonstrate risk factors for Parkinson's disease," Dr. William Weiner, chief of neurology at the University of Maryland's medical center, said in an email. "These studies do not prove that this is a risk factor and only show an association."

Dr. David X. Cifu of Virginia Commonwealth University suggested that patients "should do the basics of healthy living first."

He also argued that the risk reduction seen in the study, even if causative, is not clinically meaningful.

Gao and colleagues had identified 291 cases of incident Parkinson's disease among the 136,197 participants in the two prospective studies of healthcare workers. They compared responses to the studies' detailed questionnaires completed by these individuals with those from other participants.

In addition to the lifestyle-related questionnaires, the two studies also collected data from physical exams and medical histories.

Parkinson's disease incidence also appeared to be related to the amount of ibuprofen taken weekly. Participants who reported taking one or two tablets per week had no reduction in risk, while those taking three to five tablets or six or more tablets every week had significantly lower risks.

No such relationships were seen for aspirin, acetaminophen, or NSAIDs other than ibuprofen grouped together. Roughly as many participants reported taking these agents as they did ibuprofen.

When the analysis was expanded to include findings from six other prospective studies, including 2,779 Parkinson cases, with data on NSAID use, ibuprofen was still associated with lower disease risk, whereas other drugs were not.

The relative risk for Parkinson's disease in the pooled data was a 27 percent reduction, Gao and colleagues reported.

They noted that, unlike other NSAIDs and acetaminophen, ibuprofen is an agonist at PPAR-gamma receptors.

Dr. David Standaert, interim chairman of neurology at the University of Alabama at Birmingham, told MedPage Today and ABC News that the findings and the presumed mechanism were both plausible.

He said his own research had suggested that, while Parkinson's disease is probably triggered by a variety of factors, inflammation in the brain is what drives it along. "A simple way to express this is to say that inflammation does not start the fire, but it is responsible for keeping it burning," he said in an email.

But, he added, "the PPAR-gamma mechanism is a reasonable concept as well."

Another class of medications also targets PPAR-gamma -- the glitazone drugs used to treat type 2 diabetes.

A clinical trial based at the University of Rochester is now gearing up to test the PPAR-gamma theory of Parkinson's disease. Patients with early-stage disease will take pioglitazone (Actos) or placebo for 44 weeks. The trial's primary outcome measure will be disease progression according to the UPDRS rating scale.

In their editorial, Bower and Ritz agreed that the mechanism deserved a clinical trial -- and ideally with "a safer PPAR-gamma agonist" than ibuprofen.